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Abstract Micro- and nanoplastics can interact with various biologically active compounds forming aggregates of which the effects have yet to be understood. To this end, it is vital to characterize these aggregates of key compounds and micro- and nanoplastics. In this study, we examined the adsorption of the antibiotic tetracycline on four different nanoplastics, made of polyethylene (PE), polypropylene (PP), polystyrene (PS), and nylon 6,6 (N66) through chemical computation. Two separate approaches were employed to generate relevant conformations of the tetracycline-plastic complexes. In the first approach, we folded the plastic particle from individual polymer chains in the presence of the drug through multiple separate simulated annealing setups. In the second, more biased, approach, the neat plastic was pre-folded through simulated annealing, and the drug was placed at its surface in multiple orientations. The former approach was clearly superior to the other, obtaining lower energy conformations even with the antibiotic buried inside the plastic particle. Quantum chemical calculations on the structures revealed that the adsorption energies show a trend of decreasing affinity to the drug in the order of N66> PS> PP> PE. In vitro experiments on tetracycline-sensitive cell lines demonstrated that, in qualitative agreement with the calculations, the biological activity of tetracycline drops significantly in the presence of PS particles. Preliminary molecular dynamics simulations on two selected aggregates with each plastic served as first stability test of the aggregates under influence of temperature and in water. We found that all the selected cases persisted in water indicating that the aggregates may be stable also in more realistic environments. In summary, our data show that the interaction of micro- and nanoplastics with drugs can alter drug absorption, facilitate drug transport to new locations, and increase local antibiotic concentrations, potentially attenuating antibiotic effect and at the same time promoting antibiotic resistance.

The pathogenesis of many diseases, such as obesity, depression, cancer, cataract, and neurodegenerative diseases, is related to the generation of reactive oxygen species (ROS). Structures possessing radical-scavenging properties act as antioxidants and they could prevent the progression of the aforementioned diseases. Therefore, the current work was focused on the resynthesis and the antioxidant evaluation of 13 hydrazide-hydrazones. Two in vitro tests - DPPH and ABTS, were applied for the determination of the antioxidant capacities. The free-radical scavenging assays displayed that the hydrazide-hydrazone synthesized after condensation with a salicylaldehyde (5b) is the most potent antioxidant. The in vitro evaluation through the ABTS test showed that the former structure has greater antioxidant properties compared with the used standard - Trolox (6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid). In concentrations of 31 µM, the pyrrole-based structure showed 35.77% radical-scavenging effects. A possible binding conformation of the most active hydrazide-hydrazone in the active site of NADPH oxidase was visualised through docking simulations. The active amino acids involved in the stabilisation of the complexes were discussed. DFT studies demonstrated that 5b is a stable structure with good hydrogen and electron donating properties. Overall, the pyrrole-based hydrazide-hydrazone possesses promising antioxidant properties, however further in vitro/in vivo biological evaluations are required.

Melatonin, a hormone produced by the pineal gland, is widely recognized for its role in regulating sleep-wake cycles. With the increasing prevalence of sleep disorders, melatonin supplements have gained popularity as a natural remedy. Additionally, various sleep-enhancing dietary supplements combine melatonin with other active ingredients to enhance efficacy. Reliable and accurate analytical methods are essential for ensuring the quality, safety, and efficacy of these products. Reverse-phase high-performance liquid chromatography (RP-HPLC) is a powerful analytical technique widely used for the separation, identification, and quantification of compounds in complex mixtures. This article explores the development and validation of RP-HPLC methods for the analysis of melatonin, both as a single ingredient and in combination with other components in sleep-enhancing dietary supplements.

The main results of the work of the team of the Institute of Mathematics and Informatics at the Bulgarian Academy of Sciences on the research projects CLaDA-BG – the Bulgarian National Interdisciplinary Research e-Infrastructure for Resources and Technologies in Favor of the Bulgarian Language and Cultural Heritage, Part of the EU Infrastructures CLARIN and DARIAH and No KP-06-N50/4 30.11.2020 “Fourteenth Century South Slavonic Scribes and Scriptoria (Palaeographical Attribution and Online Repertorium)”, will be presented during the Information Day within the DiPP2024 conference. The main emphasis will be placed on developments and implementations of CultIS – a webbased software platform for intelligent digital management and presentation of large data sets and knowledge from the fields of culture, humanities, and social sciences.

The paper presents the research, development, and some of the major implementations to date of the web-based platform for intelligent cultural content management CultIS. It is an innovative environment providing descriptive cataloging, subject indexing, intelligent data retrieval, curation and collection development aimed at meeting the functional needs associated with the growing expectations of users of cultural institutions such as libraries, museums and other providers of cultural and historical heritage. Based on the implementations of CultIS for different purposes and contexts, not only its effectiveness, stability and reliability are tested, but the results also serve for its constant development and improvement.

The detection of pyrrole rings in numerous organic compounds with various pharmacological activities, emphasizes its huge importance in medicinal chemistry. Thus, the synthesis of pyrroles continues to arouse interest and Paal-Knorr condensation is considered to be the main synthetic route. A significant advance has been made since the MW activation was introduced in the organic synthesis which can be confirmed with the rapid growth of the published papers on that topic. Microwave irradiation is gaining popularity since faster reaction time, higher yields, easier work-up and reduced energy input can be achieved. Furthermore, it appears in numerous green chemistry protocols. The aim of the current article was to provide insights into the microwave syntheses of pyrrole derivatives, focusing on the most used synthetic approaches - Paal-Knorr, Clauson-Kaas, Barton-Zard, Hantzsch and others. The article was divided into several sections starting with the principles of the microwave organic synthesis. Thereafter the structure and the main pharmacological effects of the pyrrole derivatives were examined. Subsequently, articles describing the synthesis of pyrroles via Paal-Knorr, Hantzsch, Clauson-Kaas and Barton– Zard were discussed. All the reviewed papers conclude a significant reduction of the reaction times after MW irradiation compared to conventional heating.

Dichrorampha dinarica and Cydia suffuscana are known from their type localities only, and apart from the period of the imaginal stage, no data on their biology are known. Dichrorampha dinarica was discovered in Tomor Mountain (Albania), at a relatively long distance from its type locality. The moths were swept from inflorescences of Achillea abrotanoides (Vis.) Vis. (Asteraceae) in the base of 61.2 Alpine calcareous screes (CORINE Biotopes). The larval host plant of C. suffuscana was revealed: it is Lunaria annua L. (Brassicaceae), while all other closely related species from the C. succedana group feed on various Fabaceae. The habitat of the moth after CORINE Biotopes is the margin of 41.45 Thermophilous Alpine and peri-Alpine mixed lime forests. The moths and their habitats are described and illustrated.

Virtual screening is emerging as a highly applied technique and gained prominence as widely used method for the search and identification of potential hits, significantly reducing the time needed to discover novel and effective compounds compared to high-throughput screening. Recently, the superiority of simulations with multiple programs compared to a single software docking has been discussed. The aim of this work was to apply consensus docking, molecular mechanics/generalized Born surface area (MM/GBSA) free binding energy recalculations, and in vitro evaluations on an in-house dataset of recently synthesized pyrrole-based hydrazide-hydrazones in the search for novel acetylcholinesterase (AChE) inhibitors. Two licensed softwares – GOLD 5.3 and Glide, were employed for the virtual screenings, and several chemotherapeutic potential hits were identified. Furthermore, MM/GBSA free binding energy recalculations were provided to enhance the robustness of the in silico results. The MM/GBSA scores of the top ten pyrrole-based hydrazide-hydrazones were ranging from -60.44 to -70.93 Kcal/mol. Subsequent, in vitro evaluations of the top ranked compounds revealed that 12d exhibited the highest AChE inhibitory activity, with a 55% inhibition rate at a concentration of 10 μM. Moreover, this prominent pyrrole-based AChE inhibitor formed stable complex with the active site of the enzyme. Interactions with the active amino residues Tyr72 and Tyr286 indicated that 12d was located near the peripheral anionic site of the enzyme. Additionally, in silico ADME investigations using QikProp demonstrated that 12d possesses optimal pharmacokinetic properties. In conclusion, this study identified a novel pyrrole-based AChE inhibitor 12d through a combination of computational and experimental findings.

Two rare steppe species, Ceratoxanthis rakosyella Wieser et Huemer, 2000 and Thiodia irinae Budashkin, 1990, are reported for the first time from Bulgaria. They are found in endangered habitats in Northern Bulgaria. The species demonstrate peculiar genital morphology, which is discussed and illustrated. The moths, their habitats in Bulgaria and distribution are illustrated as well.

Abstract Acinetobacter baumannii has emerged as one of the most common extensive drug-resistant nosocomial bacterial pathogens. Not only can the bacteria survive in hospital settings for long periods, but they are also able to resist adverse conditions. However, underlying regulatory mechanisms that allow A. baumannii to cope with these conditions and mediate its virulence are poorly understood. Here, we show that bi-stable expression of the Csu pili, along with the production of poly-N-acetyl glucosamine, regulates the formation of Mountain-like biofilm-patches on glass surfaces to protect bacteria from the bactericidal effect of colistin. Csu pilus assembly is found to be an essential component of mature biofilms formed on glass surfaces and of pellicles. By using several microscopic techniques, we show that clinical isolates of A. baumannii carrying abundant Csu pili mediate adherence to epithelial cells. In addition, Csu pili suppressed surface-associated motility but enhanced colonization of bacteria into the lungs, spleen, and liver in a mouse model of systemic infection. The screening of c-di-GMP metabolizing protein mutants of A. baumannii 17978 for the capability to adhere to epithelial cells led us to identify GGDEF/EAL protein AIS_2337, here denoted PdeB, as a major regulator of Csu pili-mediated virulence and biofilm formation. Moreover, PdeB was found to be involved in the type IV pili-regulated robustness of surface-associated motility. Our findings suggest that the Csu pilus is not only a functional component of mature A. baumannii biofilms but also a major virulence factor promoting the initiation of disease progression by mediating bacterial adherence to epithelial cells.

Neurodegenerative diseases such as Parkinson’s and Alzheimer’s continue to be some of the most significant challenges in modern medicine. Recent research related to the molecular mechanisms of parkinsonism has opened up new approaches to antiparkinsonian therapy. In response to this, we present the evaluation of the potential neuroprotective and MAOA/MAOB inhibitory effects of newly synthesized hydrazones, containing a pyrrole moiety in the carboxyl fragment of the structure. The substances were studied on different brain subcellular fractions, including rat brain synaptosomes, mitochondria, and microsomes. The single application of 50 µM of each compound to the subcellular fractions showed that all substances exhibit a weak neurotoxic effect, with 7b, 7d, and 8d being the least neurotoxic representatives. The corresponding neuroprotective and antioxidant effects were also evaluated in different injury models on subcellular fractions, single out 7b, 7d, and 8d as the most prominent derivatives. A 1 µM concentration of each molecule from the series was also studied for potential hMAOA/hMAOB inhibitory effects. The results revealed a lack of hMAOA activity for all evaluated structures and the appearance of hMAOB effects, with compounds 7b, 7d, and 8d showing effects similar to those of selegiline. The best hMAOB selectivity index (>204) was determined for 7d and 8d, distinguishing these two representatives as the most promising molecules for further studies as potential selective MAOB inhibitors. The performed molecular docking simulations defined the appearance of selective MAOB inhibitory effects based on the interaction of the tested molecules with Tyr398, which is one of the components of the aromatic cage of MAOB and participated in π–π stabilization with the aromatic pyrrole ring. The preliminary PAMPA testing indicated that in relation to the blood–brain barrier (BBB) permeability, the tested pyrrole-based hydrazones may be considered as high permeable, except for 8a and 8e, which were established to be permeable in the medium range with −logP of 5.268 and 5.714, respectively, compared to the applied references.

Considering the complex pathogenesis of Alzheimer’s disease (AD), the multi-target ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target strategy. Thus, one novel pyrrole-based hydrazide (vh0) and four corresponding hydrazide–hydrazones (vh1-4) were synthesized by applying highly efficient MW-assisted synthetic protocols. The synthetic pathway provided excellent yields and reduced reaction times under microwave conditions compared to conventional heating. The biological assays indicated that most of the novel pyrroles are selective MAO-B inhibitors with IC50 in the nanomolar range (665 nM) and moderate AChE inhibitors. The best dual-acting MAO-B/AChE inhibitor (IC50 hMAOB–0.665 μM; IC50 eeAChE—4.145 μM) was the unsubstituted pyrrole-based hydrazide (vh0). Importantly, none of the novel molecules displayed hMAOA-blocking capacities. The radical-scavenging properties of the compounds were examined using DPPH and ABTS in vitro tests. Notably, the hydrazide vh0 demonstrated the best antioxidant activities. In addition, in silico simulations using molecular docking and MM/GBSA, targeting the AChE (PDB ID: 4EY6) and MAO-B (PDB: 2V5Z), were utilized to obtain active conformations and to optimize the most prominent dual inhibitor (vh0). The ADME and in vitro PAMPA studies demonstrated that vh0 could cross the blood–brain barrier, and it poses good lead-like properties. Moreover, the optimized molecular structures and the frontier molecular orbitals were examined via DFT studies at 6-311G basis set in the ground state.

Chrysoesthia sexguttella (Thunberg, 1794) is reported for the first time from Bulgaria. The species was found on Spinacia oleracea in Vinarovo Village, Vidin Province, Northwestern Bulgaria. Set moth and female genitalia are illustrated.

Abstract Background The process of copulation in Lepidoptera is understudied and poorly understood from a functional perspective. The purpose of the present paper is to study the interaction of the male and female genitalia of Tortrix viridana Linnaeus, 1758 via three-dimensional models of pairs fixed during copulation. Other techniques (confocal laser scanning microscopy, scanning electron microscopy and histology) were used to clarify the role of the organs involved in the process. Results Three-dimensional models based on micro-CT scanned copulating pairs were generated allowing visualisation of the position of the male and female counterparts, spatial changes during copulation, and the skeleto-muscular apparatus involved in the process. The male genitalia and their musculature are simplified in comparison with other lineages of the family, but the opposite is true for the female genitalia. The attachment of the couple is achieved only through flexion of the valvae, clasping the large and sclerotised sternite 7 of the female. The anal cone and socii of the male are in contact with certain parts of the anal papillae and the sterigma of the female. The long tubular vesica is inserted into the narrow posterior part of the ductus bursae. Its eversion is achieved by an increase in haemolymph pressure. A possible mechanism of stimulation of the female via pulsations of the diverticulum of the vesica was discovered. A compressed sclerotised area of the ductus bursae putatively serves as a valve controlling the transfer of ejaculated materials. Copulation progresses through two phases: in the first the vesica and its diverticulum are inflated by haemolymph, and in the second the diverticulum is not inflated, and the vesica is occupied by viscous ejaculated material. The formation of the multilayered spermatophore was observed, and we discovered that sperm is transferred very late in the copulation process. Conclusions Copulation process in Lepidoptera is studied for the first time with three-dimensional reconstructions of couples of Tortrix viridana, used as a model species. The internal genitalia is the scenario of multiple interactions between male and female, but the external remain static. A possible mechanism of stimulation of the female internal copulation organs is proposed.

ABSTRACTCarbapenem-resistant Acinetobacter baumannii causes one of the most difficult-to-treat nosocomial infections. Polycationic drugs like polymyxin B or colistin and tetracycline drugs such as doxycycline or minocycline are commonly used to treat infections caused by carbapenem-resistant A. baumannii. Here, we show that a subpopulation of cells associated with the opaque/translucent colony phase variation by A. baumannii AB5075 displays differential tolerance to subinhibitory concentrations of colistin and tetracycline. Using a variety of microscopic techniques, we demonstrate that extracellular polysaccharide moieties mediate colistin tolerance to opaque A. baumannii at single-cell level and that mushroom-shaped biofilm structures protect opaque bacteria at the community level. The colony switch phenotype is found to alter several traits of A. baumannii, including long-term survival under desiccation, tolerance to ethanol, competition with Escherichia coli, and intracellular survival in the environmental model host Acanthamoeba castellanii. Additionally, our findings suggest that extracellular DNA associated with membrane vesicles can promote colony switching in a DNA recombinase-dependent manner.IMPORTANCEAs a WHO top-priority drug-resistant microbe, Acinetobacter baumannii significantly contributes to hospital-associated infections worldwide. One particularly intriguing aspect is its ability to reversibly switch its colony morphotype on agar plates, which has been remarkably underexplored. In this study, we employed various microscopic techniques and phenotypic assays to investigate the colony phase variation switch under different clinically and environmentally relevant conditions. Our findings reveal that the presence of a poly N-acetylglucosamine-positive extracellular matrix layer contributes to the protection of bacteria from the bactericidal effects of colistin. Furthermore, we provide intriguing insights into the multicellular lifestyle of A. baumannii, specifically in the context of colony switch variation within its predatory host, Acanthamoeba castellanii.

Better empirical knowledge of how bat and insect phenology are influenced by seasonal environmental conditions and how this may affect fitness is essential in the face of changing climatic conditions. We examined the winter diet of the Schreibers’ bent-winged bat Miniopterus schreibersii (Kuhl, 1817) from Razhishkata Cave, Balkan Mountains, Bulgaria during four sampling periods in the winter of 2021 (end of January - end of March). We used a combination of DNA metabarcoding and a microscope-based morphological analyses of bats droppings. Additionally, we tracked prey availability in the studied area using insect flight interception traps (FIT). The species was actively feeding outside the cave and did not use the cave fauna. Our samples indicate a shift in the winter diet of the bats throughout the studied periods. Even though Diptera was the most abundant order of insects during two of the study periods, bats were preying predominantly on Lepidoptera and Hymenoptera. The metabarcoding also supported this with data for the presence of insects with diurnal activity in the samples. The temperature loggers showed a strong correlation between the outside temperature and the temperature in the cave where the colony was located, probably impacting the activity patterns of the bats. To our knowledge, this is the first study of winter bat activity and diet in Bulgaria. Our research can serve as a potential framework for studying winter bat activity and insect activity during this sensitive period.

Considering the complex pathogenesis of Alzheimer’s disease (AD), the multitarget ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target approach. Thus, a series of 13 novel (5e-q) pyrrole-based Schiff bases were synthesized by conventional and microwave-assisted condensations, and the compounds were evaluated for MAO-A, MAO-B and AChE inhibitory activities. The chemical structures of the newly formed molecules were elucidated by a combination of spectral methods. The obtained results confirmed the theoretical data. The majority of the title Schiff bases demonstrated good potential towards AChE at 10 μM concentrations, with the most promising compound 5m (58%) exerting a comparative effect to that of the applied standard—Donepezil. 5j and 5o selectively inhibited MAO-B by 26% and 21% (at 1 μM concentration), respectively. The compound condensed with 5-nitro-2-furaldehyde (5j) achieved the best dual MAO-B and AChE inhibitory capacities. In addition to the in vitro analysis, docking simulations targeting the active sites of AChE (PDB ID: 4EY6) and MAO-B (PDB: 2V5Z) were employed to explore the possible interactions of the most prominent dual inhibitor (5j) with the enzymes. Furthermore, in silico ADME and PAMPA-blood–brain barrier (BBB) studies were conducted.

In the current study, chromatographic and in silico techniques were applied to investigate the biotransformation of ethyl 5-(4-bromophenyl)-1-(2-(2-(2-hydroxybenzylidene) hydrazinyl)-2-oxoethyl)-2-methyl-1H-pyrrole-3-carboxylate (11b) in hepatocytic media. The initial chromatographic procedure was based on the employment of the conventional octadecyl stationary phase method for estimation of the chemical stability. Subsequently, a novel and rapid chromatographic approach based on a phenyl–hexyl column was developed, aiming to separate the possible metabolites. Both methods were performed on a Dionex 3000 ThermoScientific (ACM 2, Sofia, Bulgaria) device equipped with a diode array detector set up at 272 and 279 nm for analytes detection. An acetonitrile: phosphate buffer of pH 3.5: methanol (17:30:53 v/v/v) was eluted isocratically as a mobile phase with a 1 mL/min flow rate. A preliminary purification from the biological media was achieved by protein precipitation with methanol. A validation procedure was carried out, where the method was found to correspond to all ICH (Q2) and M10 set criteria. Additionally, an in silico-based approach with the online server BioTransformer 3.0 was applied in an attempt to predict the possible metabolites of the title compound 11b. It was hypothesized that four CYP450 isoforms (1A2, 2C9, 3A4, and 2C8) were involved in the phase I metabolism, resulting in the formation of 12 metabolites. Moreover, docking studies were conducted to evaluate the formation of stable complexes between 11b and the aforementioned isoforms. The obtained data indicated three metabolites as the most probable products, two of which (M9_11b and M10_11b) were synthesized by a classical approach for verification. Finally, liquid chromatography with a mass detector was implemented for comprehensive and summarized analysis, and the obtained results revealed that the metabolism of the 11b proceeds possibly with the formation of glucuronide and glycine conjugate of M11_11b.

This paper presents the development of a digital library, created for the needs of the Central Library of the Bulgarian Academy of Sciences. Based on previous work by the team from the Institute of Mathematics and Informatics at the Bulgarian Academy of Sciences, this new environment exemplifies the employment of state-of-the-art digital technologies for the presentation of scientific literary heritage, in this case the Bulgarica Collection – the advancements of the researchers in the field of Bulgarian studies in the 1980s. The development is also a component of the research e-infrastructure CLADA-BG.

In December 2019, the World Health Organization was informed of an outbreak of pneumonia of unknown etiology in Wuhan, Hubei Province, China. On January 7, 2020, a new type of coronavirus was isolated, with the WHO later officially calling it “COVID-19” and the International Committee on Taxonomy of Viruses naming the virus “SARS-CoV-2”. On January 30, 2020, the WHO declared the severe acute respiratory syndrome coronavirus 2 outbreak a public health emergency of international concern, making it an unprecedented global public health challenge. From a scientific and literary reference, it was established that the main drugs in the therapy with Covid-19 are Dexamethasone and Levofluoxetine. For this reason, we pay attention to the analysis of these two medicinal products. In the literature, we did not find an analysis of a combination of Dexamethasone and Levofloxacin. Development and validation of a highperformance liquid chromatographic analytical procedure for simultaneously determining Dexamethasone and Levofloxacin in a synthetic mixture is described in this paper. The separation was made with a LiChrosorb RP 18 (250 × 4.6 mm) column, at 25 °C temperature,with isocratic mode andmobile phase,containingt acetonitrile and woter (70-30v/v). Eluent was monitored at 254 nm and the flow rate was 1.0 ml/min. Dexamethasone and Levofluoxetine were effectively separated with retention time (tr) of 4.69 min and 14.51 min,respectively,with in the selected chromatographic conditions.The method was validated for analytical parameters: specificity, linearity, precision, accuracy,andlimits of detection and quantitation. The calibration curves were linear inthe concentration range of 12.5 to 100.0 μg/ml for Dexamethasone and Levofloxacin, and the regression coefficientswere more than 0.999. For Dexamethasone and Levofloxacin the recovery was 100.01% and 100.04%, respectively. This analytical procedure is applicable for the quality control of drug formulations.

AbstractThis study is focused on determination of the most appropriate synthetic approach for obtaining series of theophylline-7-acetyl semi- and thiosemicarbazide hybrids by using the molecular hybridization strategy with and without a catalyst. The target derivatives were further investigated for their in vitro neurotoxic and neuroprotective effects on cellular and subcellular level, along with their possible MAO-B inhibitory activities. The results identified 2-(1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-7-yl)-N-[(methylcarbamo-thioyl)amino] acetamide (5) as the most promising structure for further in vivo evaluations with the lowest neurotoxicity and the highest neuroprotection and MAO B inhibitory activity of 28%.

The subject of this communication is a funerary altar discovered in 2022 during archaeological field survey in the Sandanski area. The monument was found at site 58, situated in the locality “Saint Dimitria” near the village of Leshnitsa, municipality of Sandanski. The site is a settlement from the Roman period (2nd–4th c. AD) and the Middle Ages (13th–14th c. AD), occupying a natural, flat floodplain terrace north of the Leshnishka River, covering an area of 5.8 decares. The monument is a funerary altar, possibly exhibiting traces of an unfinished verse-inscription in Greek, dated to the second half of the 2nd c. or the beginning of the 3rd c. AD. The Leshnitsa funerary altar joins the small group of funerary epigraphy from the Middle Strymon region, whence two other examples of the same type from nearby Heraclea Sintica are also dated to the second half of the 2nd c. or the beginning of the 3rd c. AD. The funerary altar from Leshnitsa constitutes the first such example from the territory of Parthicopolis, a Trajanic or early Hadrianic foundation of AD 117–120.

Background: The pain in the lumbar region is common. One of the causes of low back pain is lumbar vertebral syndrome. There is a wide range of options for treating low back pain. The purpose of the study is to describe exercises on a balance cushion to influence the pain in lumbar vertebral syndrome and to track the effect of their application. Methods: We studied 20 participants with low back pain. We applied the following tests to the patients: visual analogue scale, Schober test, measurement of lateral flexion and Straight leg raise test. The methodology includes exercises on a balance cushion. We performed manual manipulation techniques on each patient by treating trigger points in the lower back and buttocks once a week. Results: We achieved an improvement in the studied indicators after the applied therapy, which was expressed in a reduction of pain and restoration of normal mobility in the lumbar region. Conclusions: The application of exercises on a balance cushion allows in a short time to affect the pain and mobility in the lumbar spine to fully perform their work and professional activities.

Healthy wing membranes are essential for bats. They are critical for maintaining the water balance and, during hibernation, they protect the bat’s body from dehydration. Assessing the state of the membrane visually is an easy and effective way to monitor a bat’s health and discover abnormal structures and infections in wild bat populations. During pre- and post-hibernation surveys of bats’ wings, we identified the presence of skin mites, Psorergatoides kerivoulae (Fain, 1959). The parasite causes cutaneous lesions on the wing membranes of the greater moused-eared bat, Myotis myotis (Borkhausen, 1797) and the lesser moused-eared bat, Myotis blythii (Tomes, 1857). The lesser mouse-eared bat is a new host for this parasite. Our study is the first to describe the histopathology of the infection on the wings of the greater and lesser mouse-eared bats. To our knowledge, this is the southernmost record of this parasite and the first mention of the genus Psorergatoides for the Balkans.

Klimeschia transversella (Zeller, 1839) is reported for the first time from Bulgaria. The species was found on Thymus plants in Vinarovo Village, Vidin Province, Northwestern Bulgaria. Moths and female genitalia are illustrated.

New series of 3-(1,3,7-trimethyl-xanthin-8-ylthio)propanehydrazide derivatives were designed and synthesized. The targed compounds were obtained in yields of 54 to 100% and their structures were elucidated by FTIR,1H NMR,13C NMR, MS and microanalyses. The tested compounds were subjected to in silico prediction of sites of metabolism (SOMs). The predictions show thatthe main metabolic changes will be primarily related to oxidation of the sulfur atom in the side chain, carried out under the action of CYP2C19, as well as O-demethylation of compounds containing methoxy groups.The N-demethylation of the xanthine fragment was determined to be regulated by CYP1A2, CYP2C9, CYP2D6 and CYP3A4. Theperformed in vitro studies confirmed for two of the tested compounds to be low hepatotoxic, due to the presented prooxidant effects at subcellular level (isolated rat liver microsomes). These results highlight these molecules as promising hydrazide-hydrazone structures for the design of compounds with low hepatotoxicity.

Neurodegenerative diseases such as Parkinson's and Alzheimer's continue to be some of the most significant challenges in modern medicine. Recent research related to the molecular mechanisms of parkinsonism has opened up new approaches to antiparkinsonian therapy. In response to this, we present the evaluation of the potential neuroprotective and MAOA/MAOB inhibitory effects of newly synthesized hydrazones, containing a pyrrole moiety in the carboxyl fragment of the structure. The substances were studied on different brain subcellular fractions, including rat brain synaptosomes, mitochondria, and microsomes. The single application of 50 µM of each compound to the subcellular fractions showed that all substances exhibit a weak neurotoxic effect, with 7b, 7d, and 8d being the least neurotoxic representatives. The corresponding neuroprotective and antioxidant effects were also evaluated in different injury models on subcellular fractions, single out 7b, 7d, and 8d as the most prominent derivatives. A 1 µM concentration of each molecule from the series was also studied for potential hMAOA/hMAOB inhibitory effects. The results revealed a lack of hMAOA activity for all evaluated structures and the appearance of hMAOB effects, with compounds 7b, 7d, and 8d showing effects similar to those of selegiline. The best hMAOB selectivity index (>204) was determined for 7d and 8d, distinguishing these two representatives as the most promising molecules for further studies as potential selective MAOB inhibitors. The performed molecular docking simulations defined the appearance of selective MAOB inhibitory effects based on the interaction of the tested molecules with Tyr398, which is one of the components of the aromatic cage of MAOB and participated in π–π stabilization with the aromatic pyrrole ring. The preliminary PAMPA testing indicated that in relation to the blood–brain barrier (BBB) permeability, the tested pyrrole-based hydrazones may be considered as high permeable, except for 8a and 8e, which were established to be permeable in the medium range with −logP of 5.268 and 5.714, respectively, compared to the applied references. [ABSTRACT FROM AUTHOR]

Considering the complex pathogenesis of Alzheimer's disease (AD), the multi-target ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target strategy. Thus, one novel pyrrole-based hydrazide (vh0) and four corresponding hydrazide–hydrazones (vh1-4) were synthesized by applying highly efficient MW-assisted synthetic protocols. The synthetic pathway provided excellent yields and reduced reaction times under microwave conditions compared to conventional heating. The biological assays indicated that most of the novel pyrroles are selective MAO-B inhibitors with IC50 in the nanomolar range (665 nM) and moderate AChE inhibitors. The best dual-acting MAO-B/AChE inhibitor (IC50 hMAOB–0.665 μM; IC50 eeAChE—4.145 μM) was the unsubstituted pyrrole-based hydrazide (vh0). Importantly, none of the novel molecules displayed hMAOA-blocking capacities. The radical-scavenging properties of the compounds were examined using DPPH and ABTS in vitro tests. Notably, the hydrazide vh0 demonstrated the best antioxidant activities. In addition, in silico simulations using molecular docking and MM/GBSA, targeting the AChE (PDB ID: 4EY6) and MAO-B (PDB: 2V5Z), were utilized to obtain active conformations and to optimize the most prominent dual inhibitor (vh0). The ADME and in vitro PAMPA studies demonstrated that vh0 could cross the blood–brain barrier, and it poses good lead-like properties. Moreover, the optimized molecular structures and the frontier molecular orbitals were examined via DFT studies at 6-311G basis set in the ground state. [ABSTRACT FROM AUTHOR]

Application of seismic isolation devices is an efficient way for designing seismically resistant structures. For that purpose, various types of seismic isolation devices are developed. The main differences between them are in the materials used for their production and in the way they provide horizontal flexibility. Dynamic analysis of a base isolated structure requires an adequate mathematical model of the seismic isolation devices which can describe their mechanical properties in horizontal and vertical directions. The paper is considering analytical models used for the prediction of mechanical properties in the horizontal direction of lead-rubber bearings, which are proposed in the contemporary literature. Results obtained using these analytical formulas are compared with the results obtained by the finite element analysis model developed in this paper, as well as with available test results provided by the manufacturer. Improvements of the existing analytical models are suggested in order to enable a better prediction of mechanical characteristics in the horizontal direction of lead-rubber bearings.

Base isolation of buildings is the most efficient way of designing seismically resistant structures. Application of seismic isolators allows mutually independent movements of the ground and the structure during earthquakes. The application of seismic isolators increases the natural period of vibrations, which reduces the seismic forces in the structure. The paper analyzes the influence of the application of lead rubber bearings on the response of the structure to the action of an earthquake. A reinforced concrete frame structure was analyzed both for the case of base isolation and rigid foundation. Based on the comparative analysis of the natural period of vibrations, base shear seismic forces, displacement of the top level of the structure and relative inter-storey drift, conclusions were drawn about the efficiency of application of this type of seismic isolator. The required amount of ductility of a structure, as well as damage to structural and non-structural elements, is greatly reduced by base isolation.

The current study is focused on investigation and quantitation of seven commercially available on the Bulgarian market food supplements, containing multivitamin mixtures of water-soluble and fat-soluble vitamins. In addition, a second fermentation brewer’s yeast is also analyzed. The analytical procedures are performed on a RP-HPLC/DAD using Purospher STAR C18 (Merck Millipore, Germany) 5 μm, 25 × 0.46 cm column, conditioned at 25 °C in a column oven. Dionex UltiMate 3000 high performance liquid chromatograph was carried out in diode array detector, set up at 270 nm for water-soluble vitamins, except for vitamin B5, where 210 nm was applied as analytical wavelength. The fat-soluble vitamins were detected at 325 nm and 265 nm for vitamin A and vitamin E, respectively. Two general methods were developed where Method 1 was based on gradient elution and Method 2 was based on isocratic elution. Both methods identified stated by the manufacturer labeled amounts. The developed methods are applicable for routine analysis of vitamin contents both in multivitamin preparations and in brewer’s yeast from secondary fermentation.

In this study, one novel N-pyrrolyl carboxylic acid (3), the corresponding N-pyrrolyl hydrazide (5), and four new hydrazide-hydrazones (5a-d) bearing electron donating moieties were designed, synthesized, and fully elucidated by 1H NMR, FT-IR, and HRMS. The hydrazide-hydrazones were produced in five steps, which were optimized by applying microwave heating. The microwave-assisted synthesis significantly decreased the reaction times and increased the yields of the title molecules. In addition, all novel compounds were assessed for their radical scavenging properties by employing DPPH and ABTS assays. The most promising agent was obtained after condensation of the title hydrazide (5) with a 3,5-dimetoxy-4-hydroxybenzaldehyde (5d). The latter compound showed better antioxidant properties than Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) and could serve as a prominent lead structure for future optimization as an antioxidant agent. A possible binding conformation of 5d in the active site of NADPH oxidase was also identified through molecular docking simulations. Analysis of the major interactions showed the importance of the hydroxyl moiety for the antioxidant activity. Finally, the virtual calculations of the ADME properties of the synthesized compounds displayed good drug-like properties. Overall, an optimized synthetic protocol through MW irradiation was employed. The newly synthesized ethyl (E)-5-(4-bromophenyl)-1-(1-(2-(4-hydroxy-3,5-dimethoxybenzylidene)hydrazineyl)-3-(1H-indol-3-yl)-1-oxopropan-2-yl)-2-methyl-1H-pyrrole-3-carboxylate (5d) was found to possess the most prominent radical-scavenging capacity, which identifies it as a promising lead compound for the development of novel antioxidants.